A mutation research facility capable of assessing several aspects of somatic cell mutation in diploid human cells has been developed. A system recently co-developed by the applicant to detect mutation to 8- azaguanine (AG) resistance in fibroblasts is being exploited in quantitatively assessing x-ray induced mutation in cultured, diploid human cells, and in environmental monitoring for other agents potentially mutagenic to human genetic material. Improvements of the system are being made to allow detection in vitro of low order mutagenesis. Derived mutant cells will be isolated and their phenotypes characterized with particular reference to mechanisms of somatic cell drug resistance to purine analogues. A demonstration of the utility of this system as a screening test for potential environmental carcinogens is proposed. New markers in human cells are being sought. Direct assay systems to detect infrequent AG resistant lymphocytes in blood will be utilized to detect females heterozygous for the Lesch- Nyhan (L-N) and X-linked gout mutations. An insensitive system is now available but the development of viral infective and autoradiographic methods potentially capable of detecting AG resistant lymphocytes with much greater sensitivity are being developed. Patients receiving potentially mutagenic drugs will be monitored for changes in AG resistant lymphocyte frequencies and results correlated with tests of in vitro mutagenicity of the same drug. Also, general environmental monitoring to detect increases in in vivo mutant cell frequencies is proposed. Patients on long-term purine analogue chemotherapy will also be monitored. A proposal is made that changes in AG resistant lymphocyte frequencies may form the basis for a rational sequential chemotherapy program. Finally, an enumerative assay may detect mutant lymphocytes induced in vitro. A comparative study of the in vitro mutability of two human somatic cell types is then proposed.